Steven Yukl, MD, of the University of California San Francisco, spoke (in the last presentation of the meeting) on "Challenges inherent in detecting HIV persistence during potentially curative interventions." That sounds a bit bland, I agree, especially since it has sparked a debate about whether the only HIV "cure" so far reported is actually real.

Yukl was reporting on a series of investigations by several labs, undertaken with the cooperation of the so-called Berlin Patient. You'll recall that Timothy Brown was HIV-positive when he developed leukemia while living in Berlin. His doctors there decided to give him a bone marrow transplant, but with a twist -- they selected a donor whose CD4-positive T cells did not have a key entry point used by HIV.

Technically, the donor was homozygous for the delta-32 mutation in the gene for the CCR5 receptor.

To make the story short, Brown was eventually cured of leukemia by the treatment. And -- the central point -- his new immune system bars the door to HIV.

Put another way, he no longer takes antiretroviral drugs and has no clinical signs of HIV infection.

But is he "cured?"

That depends on what you mean by "cure," and that is what Yukl and colleagues were trying to figure out.

Five years after the transplant, with Brown's cooperation, several labs looked at his plasma, peripheral blood mononuclear cells, and samples from the gut and cerebrospinal fluid to see just what, if any, signs of HIV they could find.

Bottom line: they found some scraps of HIV in some samples.

But:

Two labs looked for HIV that could replicate. Neither was successful, suggesting that if there is any replication-competent HIV in Brown's body, it is vanishingly rare -- less than one infected cell per 1.4 billion CD4+ T cells.

Some labs sometimes detected very low levels of HIV RNA in plasma,
but their genetic sequences were different from each
other and different from those present before the transplant.

Tests for HIV DNA in plasma ruled out its presence at more than one copy per two million CD4 cells.

Very
low levels of HIV DNA but not RNA were found in cells from a rectal biopsy, but there was not enough to generate genetic sequences.

Antibodies to HIV were low and declined over about 18 months.

Taken together, Yukl concluded, the data make it "impossible to conclude that the subject remains HIV-infected" -- largely because the testing is pushing the limits of the current technology.

That didn't stop Alain Lafeuillade, MD, PhD, of General Hospital in Toulon, France, from issuing a press release and suggesting online that a) Brown had never really been cured or b) he had been reinfected.

Yukl himself told Science magazine's Jon Cohen that "there are some signals of the virus."

But he added that "we don't know if they are real
or contamination, and, at this point, we
can't say for sure whether there's been complete eradication of
HIV."

The idea of the presentation was to help define what is meant by an HIV cure, he said, and to emphasize that using such sensitive tests opens the door to artifacts of the process. "At this level of detection, how do we know the signal is real?"

But the blogosphere, by and large, appears to agree that the question is moot. Whether HIV is still present or not, it's not active. To all intents and purposes Brown is cured -- he is not on medications and there are no signs of HIV infection, either clinically or in terms of replication-competent virus.

North American Correspondent for MedPage Today, is a three-time winner of the Science and Society Journalism Award of the Canadian Science Writers' Association. After working for newspapers in several parts of Canada, he was the science writer for the Toronto Star before becoming a freelancer in 1994. His byline has appeared in New Scientist, Science, the Globe and Mail, United Press International, Toronto Life, Canadian Business, the Toronto Star, Marketing Computers, and many others. He is based in Toronto, and when not transforming dense science into compelling prose he can usually be found sailing.

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